13-100532413-C-G

Variant names:

• chr13-100532413-C-G
• rs926172465
• NM_001195087.2:c.179G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001195087.2(GGACT):​c.179G>C​(p.Gly60Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G60E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GGACT NM_001195087.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54
• Publications: 0 publications found

Genes affected

GGACT (HGNC:25100): (gamma-glutamylamine cyclotransferase) The protein encoded by this gene aids in the proteolytic degradation of crosslinked fibrin by breaking down isodipeptide L-gamma-glutamyl-L-epsilon-lysine, a byproduct of fibrin degradation. The reaction catalyzed by the encoded gamma-glutamylaminecyclotransferase produces 5-oxo-L-proline and a free alkylamine. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.826

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195087.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGACT	NM_001195087.2	MANE Select	c.179G>C	p.Gly60Ala	missense	Exon 3 of 3	NP_001182016.1	Q9BVM4
	GGACT	NM_033110.3		c.179G>C	p.Gly60Ala	missense	Exon 2 of 2	NP_149101.1	Q9BVM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGACT	ENST00000683975.1	MANE Select	c.179G>C	p.Gly60Ala	missense	Exon 3 of 3	ENSP00000508020.1	Q9BVM4
	GGACT	ENST00000455100.2	TSL:1	c.179G>C	p.Gly60Ala	missense	Exon 2 of 2	ENSP00000410449.1	Q9BVM4
	GGACT	ENST00000376250.6	TSL:3	c.179G>C	p.Gly60Ala	missense	Exon 3 of 3	ENSP00000365426.1	Q9BVM4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397782 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689470

African (AFR) AF: 0.00 AC: 0 AN: 31578

American (AMR) AF: 0.00 AC: 0 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25150

East Asian (EAS) AF: 0.00 AC: 0 AN: 35724

South Asian (SAS) AF: 0.00 AC: 0 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078612

Other (OTH) AF: 0.00 AC: 0 AN: 57952

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.5
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.63		Gain of catalytic residue at R61 (P = 0.0311)
MVP		0.21
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.91
gMVP		0.90
Mutation Taster		=8/92	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs926172465; hg19: chr13-101184667;